Malaria, particularly disease caused by Plasmodium falciparum, remains one of the world's major health problems. An effective malaria vaccine is urgently needed, and the identification of malarial proteins as potential vaccine components is an important goal. This project is directed toward the biochemical and immunological characterization of two related malarial proteins, SERA and SERPH. Both proteins are located on the parasitophorous vacuole and have important similarities in sequence with cysteine proteinases. SERA has also been shown to be a protective antigen. However, the biological functions of the two proteins and the specific immune responses they elicit upon malarial infection or immunization are unknown. The hypotheses to be tested in this project are first, that SERPH and/or SERA are cysteine proteinases required for erythrocyte rupture and/or invasion by malaria parasites, and second, that due to their required proteolytic functions, these proteins contain well conserved antigenic domains that are appropriate components of a malaria vaccine. Specific aims of the project are (1) the cloning and characterization of SERA and SERPH genes from human and murine malaria parasites, (2) the biochemical analysis of SERA and SERPH expression products to determine if the proteins are cysteine proteinases as predicted, and (3) the detailed characterization of immune responses against SERA, SERPH, and portions of these proteins after malaria infection and after immunization of experimental animals. The long-term objective of the project is to determine the biological roles and immunological importance of SERA and SERPH. If epitopes within highly conserved "proteinase domains" of the proteins are found to be immunogenic, these epitopes will be of great interest as potential components of a multisubunit malaria vaccine.